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In physiological conditions, the differentiation of bone\u2010resorbing osteoclasts is delicately regulated by the balance between osteoclastogenic and anti\u2010osteoclastogenic mechanisms. Inflammation has complex impact on osteoclastogenesis and bone destruction, and the underlying mechanisms of which, especially feedback inhibition, are underexplored. Here, we identify a novel regulatory network mediated by RBP\u2010J\/NFATc1\u2010miR182 in TNF\u2010induced osteoclastogenesis and inflammatory bone resorption. This network includes negative regulator RBP\u2010J and positive regulators, NFATc1 and miR182, of osteoclast differentiation. In this network, miR182 is a direct target of both RBP\u2010J and NFATc1. RBP\u2010J represses, while NFATc1 activates miR182 expression through binding to specific open chromatin regions in the miR182 promoter. Inhibition of miR182 by RBP\u2010J servers as a critical mechanism that limits TNF\u2010induced osteoclast differentiation and inflammatory bone resorption. Inflammation, such as that which occurs in RA, shifts the expression levels of the components in this network mediated by RBP\u2010J\/NFATc1\u2010miR182\u2010FoxO3\/PKR (previously identified miR182 targets) towards more osteoclastogenic, rather than healthy conditions. Treatment with TNF inhibitors in RA patients reverses the expression changes of the network components and osteoclastogenic potential. Thus, this network controls the balance between activating and repressive signals that determine the extent of osteoclastogenesis. These findings collectively highlight the biological significance and translational implication of this newly identified intrinsic regulatory network in inflammatory osteoclastogenesis and osteolysis.<\/jats:p>","DOI":"10.1096\/fj.201902227r","type":"journal-article","created":{"date-parts":[[2019,12,23]],"date-time":"2019-12-23T05:59:31Z","timestamp":1577080771000},"page":"2392-2407","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Regulatory network mediated by RBP\u2010J\/NFATc1\u2010miR182 controls inflammatory bone resorption"],"prefix":"10.1096","volume":"34","author":[{"given":"Kazuki","family":"Inoue","sequence":"first","affiliation":[{"name":"Arthritis and Tissue Degeneration Program and David Z. 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